Glucocorticoids Regulate Bone Marrow B Lymphopoiesis After Stroke

Circ Res. 2019 Apr 26;124(9):1372-1385. doi: 10.1161/CIRCRESAHA.118.314518.


Rationale: After a stroke, patients frequently experience altered systemic immunity resulting in peripheral immunosuppression and higher susceptibility to infections, which is at least partly attributed to lymphopenia. The mechanisms that profoundly change the systemic leukocyte repertoire after stroke are incompletely understood. Emerging evidence indicates that stroke alters hematopoietic output of the bone marrow.

Objective: To explore the mechanisms that lead to defects of B lymphopoiesis after ischemic stroke.

Methods and results: We here report that ischemic stroke triggers brain-bone marrow communication via hormonal long-range signals that regulate hematopoietic B lineage decisions. Bone marrow fluorescence-activated cell sorter analyses and serial intravital microscopy indicate that transient middle cerebral artery occlusion in mice arrests B-cell development beginning at the pro-B-cell stage. This phenotype was not rescued in Myd88-/- and TLR4-/- mice with disrupted TLR (Toll-like receptor) signaling or after blockage of peripheral sympathetic nerves. Mechanistically, we identified stroke-induced glucocorticoid release as the main instigator of B lymphopoiesis defects. B-cell lineage-specific deletion of the GR (glucocorticoid receptor) in CD19-Cre loxP Nr3c1 mice attenuated lymphocytopenia after transient middle cerebral artery. In 20 patients with acute stroke, increased cortisol levels inversely correlated with blood lymphocyte numbers.

Conclusions: Our data demonstrate that the hypothalamic-pituitary-adrenal axis mediates B lymphopoiesis defects after ischemic stroke.

Keywords: glucocorticoids; hematopoietic stem cells; inflammation; lymphocyte; stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / blood*
  • Aged
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Bone Marrow / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Female
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Lymphopoiesis*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology
  • Receptors, Glucocorticoid / blood*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Stroke / blood*
  • Stroke / genetics
  • Stroke / physiopathology


  • Adrenal Cortex Hormones
  • Receptors, Glucocorticoid